大网膜联合组织工程心肌移植改善心肌梗死后大鼠心功能

目的 将骨髓间充质干细胞(MSCs)种植于共聚乙交酯-丙交酯(PLGA)补片上构建组织工程心肌(EHT),在大鼠心肌梗死模型上观察大网膜增加EHT血供,改善微环境后对心脏间质胶原重塑及心功能的影响,为心肌梗死的外科治疗提供新的途径. 方法 结扎SD大鼠左冠状动脉,制作心肌梗死模型.以大鼠MSCs为种子细胞构建EHT,将符合心肌梗死标准的18只鼠随机分成3组,每组6只,A组:网膜包裹EHT;B组:单纯EHT移植;对照组:单纯心肌梗死;另设假手术组(n=6):仅开胸,不结扎冠状动脉及EHT移植.EHT植入后4周,用二维超声心动图检测心功能,彩色室壁运动(CK)方法检测梗死部位心室壁运动,取标本做天狼猩红染色在光学显微镜下观察心肌改变. 结果 A组EHT植入后4周部分PLGA纤维降解,梗死部位心肌间质胶原含量较B组和对照组明显减少(P<0.05).CK检查显示A组梗死部位心室壁运动较B组和对照组明显改善(P<0.05);A组左心室收缩期末内径(LVESD)和左心室舒张期末内径(LVEDD)较对照组和B组明显减小(P<0.05),左心室射血分数(LVEF)、左心室缩短分数(LVFS)较对照组和B组明显增大(P<0.05). 结论 大网膜包裹MSCs-PLGA构建的EHT覆盖于梗死心肌表面能改善心肌梗死后间质胶原重塑和梗死部位心室壁运动,有利于心功能的恢复.     

组织工程心肌补片对黑山羊陈旧性心肌梗死心功能和建立侧支循环的影响

目的探讨自体骨髓间充质干细胞(m arrow m esenchym a l stem ce lls,M SC s)-小肠黏膜下层(sm a llin testina l subm ucosa,S IS)构建的组织工程心肌补片,移植于陈旧性心肌梗死区后对心功能及缺血区建立侧支循环的影响。方法将已建立急性心肌梗死模型后6周的黑山羊16只,随机分为实验组和对照组,实验组抽取自体骨髓,经体外分离M SC s,进行培养、传代,以第3代细胞行5-B rdU标记并与S IS支架材料复合培养5 d,制备M SC s-S IS组织工程心肌补片。将其缝合至陈旧性心肌梗死区;对照组仅行假手术处理。于植入后6周,采用超声心动图观察两组动物心功能变化,数字减影血管造影选择性左冠状动脉造影观察缺血心肌侧支循环的建立。结果术后6周实验组及对照组:心博出量、左心室射血分数分别为42.81±4.91、37.06±4.75 m l和59.20%±5.41%和44.56%±4.23%,组间差异均有统计学意义(P<0.05);左心室舒张末期容积、左室收缩末期容积分别为72.55±8.13、83.31±8.61 m l和29.75±5.98、46.25±6.68 m l,组间差异均有统计学意义(P<0.05);左心室舒张功能各项指标分别为:E峰最大速度分别为54.85±6.35 cm/s和43.14±4.81cm/s(P<0.01);A峰最大速度分别为52.33±6.65 cm/s和56.91±6.34 cm/s(P>0.05)。超声心动图显示对照组左室腔扩张明显,室壁运动明显减弱,梗死区呈瘤样扩张,局部室壁反常运动;实验组左室腔明显小于对照组,室壁运动较对照组强,心尖梗死区扩张不明显。选择性左冠状动脉造影见实验组左冠状动脉前降支远端与回旋支间明显侧支循环建立。结论M SC s-S IS构建的组织工程心肌补片移植于黑山羊陈旧性心肌梗死区后侧支循环建立,心功能有明显改善作用。     

骨髓间质干细胞移植梗死心肌后细胞因子分泌及对血管新生的影响

目的研究骨髓间质干细胞(MSCs)移植梗死心肌后细胞因子的分泌及其对血管新生的作用.方法贵州香猪24只,按照计算器随机数法随机分为对照组、实验组.抽取骨髓液3 ml,按照Wakitani的方法培养出骨髓间质干细胞,经5-氮胞苷(5-aza)诱导后,5-溴脱氧尿苷(BrdU)标记备用.开胸结扎左冠状动脉前降支,自体骨髓间质干细胞分别经局部注射和结扎的左冠状动脉前降支远端灌注移植入自体急性心肌梗死区域,对照组以DMEM作对照.术后3周、6周取标本,免疫组织化学法、计算机图象分析检测组织血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)和Ⅷ因子表达.结果实验组梗死区3周、6周bFGF、VEGF灰度值明显高于对照组(P<0.01),微血管计数明显增多(P<0.01).结论自体骨髓间质干细胞移植梗死心肌后能分泌VEGF、bFGF,诱导血管新生.     

Cx43转基因自体成肌细胞移植对犬急性心肌梗死后心肌结构和心功能的影响

目的移植Cx43转基因自体成肌细胞(Cx43 SMC)到犬急性心肌梗死(AMI)区内,观察移植Cx43 SMC对心肌结构和心功能的影响。方法将24条健康杂种犬采用计算器随机法分为3组(n=8),即成肌细胞(SMC)移植组、Cx43 SMC移植组和对照组。取犬自体骨骼肌,经体外分离、培养和转化,将质粒载体pLenti6/V5-DEST-Cx43转入骨骼肌成肌细胞。利用结扎左前降支(LAD)的方法建立AMI动物模型,经LAD和梗死区多点注射的方法将实验组犬注射SMC或Cx43 SMC(细胞总数2×10~6个),对照组注射等量的细胞培养液。分别在AMI前1d、AMI后4周、细胞移植4周后,用超声心动图(UCG)测量左室射血分数(LVEF)、左室舒张末期内径(LVDD)和左室收缩末期内径(LVSD)；并进行心肌组织的光镜和电镜的病理学检查。结果AMI前UCG检查犬左室形态和收缩功能正常,结扎LAD 4周后,LVEF降低、LVDD和LVSD均增加(P＜0．05)。移植后4周,与对照组和移植前比较,SMC和Cx43 SMC移植组的LVEF升高、LVDD和LVSD减少(P＜0．05),其中Cx43 SMC移植组较SMC移植组为显著(P＜0．05)。组织病理学检查亦显示移入的Cx43 SMC在宿主心肌组织中排列有序,与宿主心肌细胞的排列方向一致,其间有闰盘形成。结论Cx43 SMC梗死区心肌移植后可减轻心室重构的进程,增加心肌的收缩力,改善心功能。     

骨髓基质干细胞治疗兔缺血心肌的初步实验研究

目的通过建立兔自体骨髓移植模型,验证骨髓基质干细胞(MSCs)移植到缺血心肌后是否在心肌的微环境中可以向心肌细胞分化,探讨其对缺血心肌心功能的影响。方法将13只新西兰大白兔分为实验组(7只)和对照组(6只),实验组于心肌梗死前后缘上、中、下各3点分别注射被5溴-2脱氧尿苷(BrdU)标记的自体MSCs(3×106cells/30μl);对照组注射同等量的磷酸盐缓冲液(PBS)。移植4周后通过激光共聚焦显微镜验证移植后的MSCs是否向心肌细胞分化,并用心脏彩色超声心动图和多导生理记录仪测定缺血心肌的心功能。结果移植4周后,MSCs向心肌细胞分化,表达出α-肌小节肌动蛋白(-αsarcomeric actin)和存在于闰盘中的连接蛋白43(connexin 43),自体MSCs能够增加局部心肌组织中血管数量。实验组心肌左心室收缩功能明显比对照组增强[左心室射血分数(LVEF):0.51±0.07 vs.0.43±0.06,左心室侧壁运动幅度(LVLWMD):1.75±0.42mm vs.1.09±0.28mm,左心室收缩期室壁增厚率(LVΔT):0.19%±0.05%vs.0.11%±0.04%,左心室收缩压(LVSP):113.1±6.3 mmHg vs.99.5±5.1 mmHg,左心室舒张期末压(LVEDP):11.5±2.1 mmHg vs.14.3±3.1mmHg,左心室压力增高最大速率(+dp/dtmax):4 618.3±365.2mmHg/s vs.3 268.1±436.9 mmHg/s,左心室压力下降最大速率(-dp/dtmax):3 008.8±346.7mmHg/s vs.2 536.9±380.4 mmHg/s,P<0.05]。结论自体MSCs移植到兔缺血心肌后可以向心肌细胞分化,提高缺血心肌的心功能,对治疗心肌缺血具有较好的前景。     

犬急性心肌梗死早期冠状动脉旁路移植术对左室壁运动的影响

目的 探讨犬急性心肌梗死早期冠状动脉旁路移植术对室壁运动的影响及其在唤醒冬眠心肌中的意义.方法 结扎犬冠状动脉前降支制备心肌梗死模型(30只).按手术日期随机分组,分别在心肌梗死后1、2、4、6周行冠状动脉旁路移植术作为实验组,其中第2周4只,其余每组6只;对每个实验组分别设立心肌梗死对照组(不进行冠状动脉旁路移植术),每组2只.实验组在冠状动脉旁路移植术前及冠状动脉旁路移植术8周后开胸利用多巴酚丁胺超声负荷试验结合组织多普勒成像技术标记冬眠心肌,并测定室壁运动记分;对照组在相同时间点同样的方法标记冬眠心肌并测定室壁运动记分.每只犬处死后分别测定心肌梗死面积.结果 每个实验组各存活4只,对照组均存活.1、2周实验组较4、6周实验组及对照组梗死区心肌室壁运动记分的变化明显减小(0.03±0.06,0.05 ±0.09,0.23 ±0.08,0.27±0.06,0.32 ±0.05,P＜0.05),所有实验组较对照组心肌室壁运动记分的变化明显减小(1.195±0.09,1.25±0.18,1.30±0.18,1.36 ±0.11,1.65 ±0.17,P＜0.05),所有实验组较对照组唤醒更多的冬眠心肌(0.27 ±0.12,0.22±0.04,0.31±0.09,0.23±0.03,0.03 ±0.04,P＜0.05).1、2周实验组较4、6周实验组及对照组心肌梗死范围明显减小[(20.75±2.63)％,(21.25±2.5)％,(27.25±1.71)％,(27.75±2.22)％,(26.50±0.71)％,(29.00±1.41)％,(27.00±1.41)％,(28.50±0.71)％,P＜0.05)].结论 犬急性心肌梗死早期冠状动脉旁路移植可以明显改善心肌室壁运动,唤醒更多的冬眠心肌,尤其2周内行冠状动脉旁路移植术可以最大限度地减少梗死心肌对室壁运动的影响,并可以减少心肌梗死范围.     

骨髓间充质干细胞自体移植治疗心肌梗死的实验研究

目的探讨兔骨髓间充质干细胞(MSCs)移植至缺血心肌后的增殖分化情况,对缺血心肌细胞的修复重建能力及心功能改善情况。方法将20只新西兰白兔随机分为骨髓间充质干细胞移植组(MSCs组,n=10)和对照组(n=10),采用结扎冠状动脉左前降支(LAD)制备心肌梗死模型,2周后分别将Dil标记的1×106个细胞悬液400μl或等量L-DMEM培养基用微量注射器注入梗死灶边缘,于建模前、建模后2周、细胞移植后2、4周采用多普勒超声心动图检测左心室收缩期末内径(LVESD)、左心室舒张期末内径(LVEDD),计算左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)评价心脏收缩功能,同时进行心肌声学造影评价心肌组织的血流灌注情况。细胞移植后8周处死所有动物,病理学检查移植细胞在梗死区的生长状况。结果多普勒超声心动图检测结果显示:两组动物建模前、建模后2周LVEF、LVFS差异无统计学意义(0.72±0.08vs.0.71±0.04,0.56±0.11vs.0.55±0.09;0.35±0.06vs.0.35±0.04,0.24±0.08vs.0.23±0.03,P>0.05),细胞移植后2、4周MSCs组LVEF、LVFS值均明显高于对照组(0.71±0.05vs.0.60±0.05,0.72±0.07vs.0.62±0.08;0.34±0.03vs.0.29±0.01,0.35±0.06vs.0.27±0.05,P<0.05);病理学检查见自体MSCs移植8周后存活于梗死心肌中,表达肌细胞特异性标志,并且能显著增加瘢痕区毛细血管密度(38.6±7.6/mm2vs.21.4±3.9/mm2,P<0.05),心肌声学造影亦显示梗死局部血流灌注MSCs组较对照组明显改善。结论自体MSCs移植缺血心肌中可向心肌细胞分化,增加心肌血流灌注,改善心脏收缩功能。     

3种不同途径移植自体骨髓间充质干细胞治疗急性心肌梗死效果比较

目的比较3种不同途径移植自体骨髓间充质干细胞(MSCs)治疗急性心肌梗死效果。方法小型猪12只,建立心肌梗死(AMI)模型,纯化扩增并将DAPI标记的MSCs经冠脉、心内膜及心外膜注射移植,移植前后记录左室血流动力学指标及LVEF变化,3个月后取心肌行免疫组织化学检测结蛋白desmin和心肌特异性肌钙蛋白I(cTnI)的表达。结果冠脉组梗死心肌周围未见明确的移植细胞,仅见非特异的荧光染色,与心梗后比较心功能改善,但与对照组比较无明显差异;心内膜及心外膜组移植的MSCs分布较广,胞核为蓝色椭圆形,免疫组织化学检测胞浆心肌特异蛋白染色阳性,与冠脉移植组比较LVEDP降低(P<0．05)、LV±dp／dtmax增快(P<0．05)、 LVEF增高(P<0．05)、新生血管数增加及瘢痕面积缩小等指标改善更明显,且有统计学意义。结论 3种途径移植MSCs均可改善AMI后心功能,经冠脉移植不是最佳途径,心肌内注射效果更好。     

窦房结细胞自体移植治疗完全性房室传导阻滞

目的 探索窦房结细胞自体移植到右室前壁心肌内,治疗心脏术后完全性房室传导阻滞的可行性.方法 取健康杂种犬20只,随机分为移植组和对照组,每组10只.安置电子心脏起搏器后,获取移植组犬窦房结组织并制成细胞悬液,经荧光标记后注射到移植组自体右心室前壁心肌内.对照组窦房结行Van Gieson染色,并与心耳肌组织比较.对照组右心室相同部位注射等量培养液.两周后射频消融希氏束,建立完全性房室传导阻滞动物模型,并进行心脏电生理研究.对移植组犬经股静脉应用异丙肾上腺素,研究心律变化.结果 急性分离的成年犬窦房结细胞多为长梭形,细胞活性好.获取的窦房结组织行Van Gieson染色后可见其典型结构特征.建立完全性房室传导阻滞犬模型1 h后,移植组心率高于对照组(P＜0.05),且此室性自主心律起源于细胞移植部位.注射异丙肾上腺素后,移植心室律变化明显(P＜0.05).结论 成年犬窦房结细胞移植到自体右室前壁心肌内,能够提高完全性房室传导阻滞后的心室律,并对异丙肾上腺素具有良好的反应性.     

猪心肌非缺血性梗死研究

目的 观察心肌非缺血性梗死发生发展的规律.方法 中国小型猪12头,体重18～20 kg,实验组结扎LAD上等流量点,对照组解剖相应部位LAD外膜(n=6),术中测定左心室心底和心尖部位血流动力学指标.4周后取出心脏标本,将左心室分成17段,4%多聚甲醛固定1周,苏木素-伊红(HE)、PATH及天狼星红染色进行病理学观察.结果 结扎LAD 4周后,左心室17段心肌内均可发现大小不等的梗死灶.左心室腔近心端收缩压收缩压[(264.05±49.34)比(168.35±31.74)mmHg(1 mm Hg=0.133 kPa)]、平均压[(128.65±33.68)比(82.86±14.45)nnnHg、发展压[(255.09±103.18)比(178.70±31.70)nnnHg]与心尖部比较差异有统计学意义(P＜0.05).结论 结扎猪左冠状动脉前降支后,左心室非缺血区域可发生局灶性梗死.     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Immunomodulation in Transplantation with Photopheresis

Abstract: Photopheresis is a technique in which peripheral blood mononuclear cells, in the presence of a photoacti-vatable compound, are exposed extracorporeally to ultraviolet A light and reinfused, inducing a host autoregula-tory immune response. Experimental work and ongoing clinical studies are helping to define the role of this novel, safe, and non-toxic immunomodulating technology in the field of transplantation.